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- Title
IL-10 Induces T Cell Exhaustion During Transplantation of Virus Infected Hearts.
- Authors
Gassa, Asmae; Fu Jian; Kalkavan, Halime; Duhan, Vikas; Honke, Nadine; Shaabani, Namir; Friedrich, Sarah-Kim; Dolff, Sebastian; Wahlersg, Thorsten; Kribben, Andreas; Hardt, Cornelia; Lang, Philipp A.; Witzke, Oliver; Lang, Karl S.
- Abstract
Background/Aims: Unexpected transmissions of viral pathogens during solid organ transplantation (SOT) can result in severe, life-threatening diseases in transplant recipients. Immune activation contributes to disease onset. However mechanisms balancing the immune response against transmitted viral infection through organ transplantation remain unknown. Methods & Results: Here we found, using lymphocytic choriomeningitis virus (LCMV), that transplantation of LCMV infected hearts led to exhaustion of virus specific CD8+ T cells, viral persistence in organs and survival of graft and recipient. Genetic depletion of Interleukin-10 (IL-10) resulted in strong immune activation, graft dysfunction and death of mice, suggesting that IL-10 was a major regulator of CD8+ T cell exhaustion during SOT. In the presence of memory CD8+ T cells, virus could be controlled. However sufficient antiviral immune response resulted in acute rejection of transplanted heart. Conclusion: We found that virus transmitted via SOT could not be controlled by naïve mice recipients due to IL-10 mediated CD8+ T cell exhaustion which thereby prevented immunopathology and graft failure whereas memory mice recipients were able to control the virus and induced graft failure.
- Subjects
HEART transplantation; VIRUS disease transmission; LYMPHOCYTIC choriomeningitis virus; INTERLEUKIN-10; PATHOGENIC viruses; T cells; IMMUNE response
- Publication
Cellular Physiology & Biochemistry (Karger AG), 2016, Vol 38, Issue 5, p1171
- ISSN
1015-8987
- Publication type
Article
- DOI
10.1159/000443067